title: A new regimen for continuous infusion of vancomycin during continuous renal replacement therapy.
abstract: BACKGROUND
  Continuous infusion (CI) of high-dose vancomycin is often used to treat life-threatening infections caused by less-susceptible Gram-positive bacteria. However, this approach has not been well studied in patients on continuous renal replacement therapy (CRRT). The aim of this study was to evaluate the adequacy of a new CI vancomycin regimen in septic patients undergoing CRRT.
  
  
  METHODS
  In this prospective study we measured vancomycin concentrations obtained with a new CI regimen for CRRT, which included a loading dose of 35 mg/kg given over a 4 h period followed by a daily dose of 14 mg/kg. Vancomycin concentrations were measured: at the end of the loading dose (T1); 12 h after the onset of therapy (T2); and 24 h after the onset of therapy (T3). Drug concentrations (at T2 and T3) were considered adequate if between 20 and 30 mg/L. CRRT intensity was calculated as: dialysate rate (mL/kg/h) + ultrafiltration rate (mL/kg/h). Vancomycin population pharmacokinetics were calculated using non-linear mixed-effects modelling.
  
  
  RESULTS
  We studied 32 patients who received median (IQR) loading and daily vancomycin doses of 2750 mg (2250-3150) and 1100 mg (975-1270), respectively. Drug concentrations were: T1, 44 mg/L (38-58); T2, 27 mg/L (24-31); and T3, 23 mg/L (19-31). Vancomycin concentrations were adequate in 22/32 patients (69%) at T2 and in 20/32 (63%) at T3. The two relevant covariates that significantly affected drug concentrations were body weight and CRRT intensity.
  
  
  CONCLUSIONS
  This new vancomycin regimen allowed the rapid achievement of target drug concentrations in the majority of patients. CRRT intensity had an influence on vancomycin clearance.
authors.affiliation: Department of Intensive Care, Hôpital Erasme, Université Libre de Bruxelles, Route de Lennik, 808, 1070 Bruxelles, Belgium.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Beumier
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
authors.forename: Hakim
authors.initials: H
authors.lastname: Kabtouri
authors.forename: Maya
authors.initials: M
authors.lastname: Hites
authors.forename: Frederic
authors.initials: F
authors.lastname: Cotton
authors.forename: Fleur
authors.initials: F
authors.lastname: Wolff
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
authors.forename: Frédérique
authors.initials: F
authors.lastname: Jacobs
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vincent
authors.forename: Fabio Silvio
authors.initials: FS
authors.lastname: Taccone
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001424:Bacterial Infections / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D011446:Prospective Studies; D017582:Renal Replacement Therapy / Q000379:methods*; D018805:Sepsis / Q000188:drug therapy*; D014640:Vancomycin / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin
keywords: loading dose; pharmacokinetics; sepsis